NOACs Tied to Slower Cognitive Decline in Comorbid AF and AD

Non-vitamin K oral anticoagulant (NOAC) use was associated with modestly slower cognitive decline among older adults with comorbid atrial fibrillation (AF) and Alzheimer’s disease (AD).According to the results of a nationwide Swedish study among more than 7000 adults, the annual decline in Mini-Mental State Examination scores was 0.23 points smaller with NOAC use vs no anticoagulant use and 0.21 points less than with warfarin use. NOAC use was also associated with lower risks for all-cause mortality, ischemic stroke or systemic embolism, and fracture compared with no anticoagulation, without a significant increase in major bleeding.Although the difference in MMSE scores was modest, it increased over time, with mean scores at 5 years of 15.3 among NOAC users compared with 14.3 among those not receiving anticoagulants.“The difference is modest for an individual patient from 1 year to the next, but over a longer period, even such an effect could influence how cognitive function develops. Our findings suggest that NOAC treatment may also be significant for cognition in this patient group,” study investigator Nanbo Zhu, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet in Stockholm, Sweden, said in a statement.The study was published online on August 12 in the European Heart Journal.The AF, AD LinkAF is often comorbid with AD in older adults, and the two conditions have been linked, even in the absence of clinically apparent stroke. Potential mechanisms include cerebral infarction, reduced cerebral perfusion, and microbleeds.Although oral anticoagulation is standard therapy for ischemic stroke and systemic embolism prevention in patients with AF, whether it slows cognitive decline after AD develops remains unclear.To determine whether oral anticoagulant use was associated with cognitive decline and major clinical outcomes in patients with both AF and AD — and whether these outcomes differed among NOACs, warfarin, and no anticoagulation — the investigators analyzed data from the Swedish Registry for Cognitive/Dementia Disorders (SveDem) linked to several national health registries.They identified patients diagnosed with incident AD or mixed AD dementia between May 2007 and December 2020 who had preexisting AF.The study included 7308 individuals (mean age at AD diagnosis, 82.6 years; 52.7% women). At baseline, 3341 patients were not receiving an oral anticoagulant, 2277 were receiving warfarin, and 1690 were receiving a NOAC.Anticoagulant use was determined from the most recent oral anticoagulant dispensed during the 4 months prior to the AD diagnosis date. Cognitive function was assessed using the MMSE at baseline and during annual follow-up visits for up to 5 years.The investigators evaluated mortality, ischemic stroke or systemic embolism, major bleeding, and fracture as clinical outcomes.A Cognitive Advantage?Compared with both no anticoagulant use and warfarin, NOAC treatment was associated with a modest but statistically significant slowing of cognitive decline.In the final adjusted model, the annual decline in MMSE score was 0.23 points smaller with NOACs than with no anticoagulant use and 0.21 points smaller than with warfarin.Cognitive decline did not differ significantly between warfarin and no anticoagulant use (beta coefficient, 0.02 points/yr). All three groups started with a predicted mean MMSE score of 21.5. After 5 years, scores were 15.3 among NOAC users compared with 14.5 among warfarin users and 14.3 among those not receiving anticoagulants.Compared with no anticoagulant use, both NOACs and warfarin were associated with lower risks for mortality and ischemic stroke or systemic embolism. The associations were stronger with NOACs (hazard ratios [HRs], 0.81 and 0.66, respectively) than with warfarin (HRs, 0.88 and 0.85, respectively).NOAC use was also associated with a lower risk for fracture (HR, 0.79), with no significant difference in major bleeding (HR, 1.05); warfarin, however, was associated with a higher risk for major bleeding (HR, 1.31).In a direct comparison with warfarin, NOAC use was associated with a lower risk for ischemic stroke or systemic embolism (HR, 0.78). Major bleeding was also less frequent with NOACs, although the difference did not reach statistical significance (HR, 0.80).At 3 years, warfarin use was associated with a 3.7% lower absolute mortality risk but a 3.1% higher absolute risk for major bleeding compared with no anticoagulant use. NOAC use was associated with a 5.9% lower absolute risk for mortality and a 4.7% lower absolute risk for ischemic stroke or systemic embolism.Mortality, Stroke, and Bleeding OutcomesCompared with warfarin, NOACs were associated with a 3.0% lower risk for ischemic stroke or systemic embolism and a 2.7% lower risk for major bleeding.The investigators proposed several potential explanations for the slower cognitive decline associated with NOAC use, including fewer cerebral infarctions, improved cerebral perfusion, and modulation of pathways involving inflammation and amyloid-beta.Still, the study’s observational design cannot determine whether NOAC treatment directly contributed to slowed cognitive decline.Other limitations included residual and unmeasured confounding, changes in anticoagulant use during follow-up, and variability in the timing and frequency of MMSE assessments. The study also did not assess individual NOAC agents. In addition, the findings may not be generalizable to other dementia subtypes.“While awaiting more evidence on cognitive outcomes, anticoagulation decisions should remain primarily guided by stroke prevention rather than anticipated cognitive benefit,” the investigators cautioned.“Overall, these findings support NOACs as preferred over warfarin in patients with AF and AD in contemporary clinical practice,” they concluded.The study was funded by the Swedish Research Council, the Swedish Brain Foundation, the Center for Innovative Medicine, ALF project funding, Karolinska Institutet internal funds, and additional Swedish foundations and research organizations. Disclosure information for study authors is available in the original study publication.